Melanie Cole, MS (Host): Welcome to Better Edge, a
Northwestern Medicine Podcast for physicians. I'm Melanie Cole. And joining me
today is Dr. Bradley Knight. He's the Director of Cardiac Electrophysiology at
Northwestern Medicine and he's the Director of the Heart Rhythm Center at the Bluhm
Cardiovascular Institute. He's here to highlight left atrial appendage closure
device options at Northwestern Medicine for us today.

Melanie Cole, MS: Dr. Knight, it's a pleasure to have
you join us. I'd like you to start by telling us a little bit about AFib and
the prevalence. What's the scope of the issue that we're discussing here today?

Dr Bradley Knight: Thank you, Melanie. Yes, atrial
fibrillation is an epidemic. We've just made it through a COVID-19 pandemic,
but I think it's important to remember how high the incidence and prevalence
are of atrial fibrillation and how it's projected to grow dramatically. About
10% of people over age 80 have atrial fibrillation. And as you can imagine, the
drivers for this increased incidence of atrial fibrillation include the aging
population and obesity. Obesity is another epidemic of its own, but it's really
driven an increase in atrial fibrillation, particularly in young patients.

Melanie Cole, MS: So then, tell us about your role at
Northwestern Medicine's Bluhm Cardiovascular Institute. I introduced you as the
Director of the Heart Rhythm Center there. Tell us a little bit about what that
means and what do you do.

Dr Bradley Knight: I've been the director of cardiac
electrophysiology here for 14 years. We have an outstanding group of
interventional electrophysiologists with nine electrophysiologists downtown,
and we have several electrophysiologists at the regional hospitals as part of
Northwestern Medicine. I work with my colleague, Dr. Al Lin, who's the Director
of the Left Atrial Appendage Closure Program. And we have been very involved in
the clinical trials that have led to the FDA approval of the left atrial
appendage closure devices.

Melanie Cole, MS: Is offering left atrial appendage
closure treatment options a priority at Northwestern Medicine? And why is that?

Dr Bradley Knight: Well, in general, our goals at
Northwestern are to have new technology available to our patients, not just to
have the technology available, but to have physicians here who have expertise
with this technology. So, we've been involved, as I mentioned, in all these
clinical trials that have led to the approval of the Amulet device and the
Watchman device. We have a lot of experience with other left atrial appendage
closure devices, suture snare devices and other closure devices. It's a
priority because it's an important therapy to offer patients.

Atrial fibrillation, as the listeners would know, increases the
risk of stroke, and these strokes can be devastating. Strokes related to atrial
fibrillation tend to be large strokes. It can result in significant disability
and mortality. And so for patients who have an indication for anticoagulation,
which includes most of our patients, who have a CHADS-VASc score of one or
higher, if they have an indication for anticoagulation, but are unable for a
reasonable reason to continue taking it long term, the alternative is really no
anticoagulation versus left atrial appendage closure. So, I think it's
important to keep in perspective, a lot of these trials were comparing these
devices and therapies to warfarin. The real clinical issue are patients who
really cannot continue long-term anticoagulation and their risk of stroke is
significantly elevated off anticoagulation. So, this is a therapy that we offer
patients. We've been offering it for over a decade as part of clinical trials
and now, for several years as part of FDA approval. And also, we've expanded
this to availability at the regional hospitals, including Central DuPage, the
Northwest region and the Palos Hospital region.

Melanie Cole, MS: Dr. Knight, I'd like you to speak
about outcomes. Have these devices been successful in lowering stroke? And when
we speak of treatment, I'd like you to speak a little bit about the problems
you're really trying to solve. We're not really curing the AFib, correct? Just
reducing the risk of stroke, rate control, anticoagulation, both. Tell us a
little bit about your outcomes, what you're trying to do here.

Dr Bradley Knight: Well, when we see patients with
atrial fibrillation, we like to focus on a few different aspects of their care.
One is heart rhythm control, whether we should restore and maintain sinus
rhythm, whether it's with antirrhythmic drugs, cardioversion or commonly
catheter ablation, which is increasingly becoming a first line therapy. We talk
about rate control, so that if they have breakthrough episodes, we can control
the rate, which often improves their symptoms and can be sufficient for some
patients. And then, we talk about the lifestyle modifications that can be done
to prevent recurrent atrial fibrillation. We talk about the obesity problem.
But there are several modifiable risk factors for atrial fibrillation,
including alcohol reduction, weight loss and treating other comorbidities. But
the emphasis really is on stroke prevention. As I mentioned, it can be really a
devastating thing when a patient has a stroke. Often the first manifestation of
atrial fibrillation is when patients present with a stroke or you're really
unaware that they had atrial fibrillation. So, our outcomes for this therapy
really are to safely and effectively implant a device that lowers the risk of
stroke. It has been shown in many clinical trials to be comparable to
anticoagulation in ischemic stroke, but the cumulative benefit of avoiding
anticoagulation includes a reduction in intracranial hemorrhage, in major
bleeding and, in some longer trials, there are some clues of a mortality
benefit from left atrial appendage closure.

Melanie Cole, MS: You've touched briefly on patient
selection. Tell us a little bit more about the criteria for determining if
these devices are appropriate for a certain patient.

Dr Bradley Knight: Yeah. So in general, patients who are
at risk for stroke who have an indication for oral anticoagulation, who have a
reasonable reason to not take it long term, are very good candidates for left
atrial appendage closure. CMS or Medicare has guidelines for reimbursement that
we follow very carefully. There are, I believe, six different criteria which
include procedural volume requirements by the physician, procedural volume
requirements by the hospital, access to a heart team, and participation in the
Left Atrial Appendage Closure Registry. You mentioned quality and outcomes and
we very carefully every quarter review our outcomes and are quite pleased to
say that our risk of major complications is about half of our other academic
medical center peers. So, it's an important therapy to offer patients, but it's
really important to keep the complication rate low, which at this point is
about 2-3%. The criteria really apply to patients who I think have a reasonable
indication to come off of it. Some patients just have a preference. There are
some trials ongoing right now for patients who don't have a real strong
indication to come off anticoagulation to see which really is better. There's
no evidence yet that appendage closure is superior to the novel or newer oral
anticoagulants. But the CHAMPION Trial and the CATALYST trial are designed just
for that reason, to randomize patients on NOACs to left atrial appendage
closure to determine if it's superior to anticoagulation for patients who can
tolerate anticoagulation. But currently, the indications are for patients who
have contraindications. These usually include bleeding, you know, multiple
falls resulting in bleeding, other intolerances to the oral anticoagulants,
intracranial hemorrhage, for example. And those are the patients we really are
focused on.

Melanie Cole, MS: You touched briefly on the different devices,
Watchman and Amulet. Tell us about those, the ones that are currently available
for this procedure and why you might choose one over the other.

Dr Bradley Knight: Well, the experience that we've had
at Northwestern has mostly been with the Watchman device, which is a plug
device. We were part of their clinical trials and currently are implanting. A
far majority of our appendage closures are with Watchman. It's a plug device.
It has five different sizes, and so we spend a lot of time making sure that we
have a stable location with adequate compression of the device without a leak.
And so, we have a lot of experience with Watchman. The alternative device
currently that's FDA approved is the Amulet made by Abbott, and we have
participated in the trials for that device as well. We tend to reserve that for
patients who have a contraindication to the Watchman based on the size or shape
of their appendage. There are some patients who have failed Watchman implants
here or elsewhere, who are referred for a closure with Amulet. And it's a
slightly different device. It's a plug and a disc. So, there's a lobe that is
in the appendage that's anchored to the inside of the appendage, and then with
a disc, that's pulled up against the face of the appendage. It's a two-part
device, so it's a little bit more complicated. It comes in seven different
sizes. But we have a lot of experience with both devices. In the past, there
was the Lariat device, which was approved only for soft tissue closure. And
once the Watchman and Amulet devices became FDA approved and commercially
available, we've had very limited implantation of this suture snare that was
being performed previously as part of the trial as well.

Melanie Cole, MS: Dr. Knight, as an electrophysiologist,
what do you find is the greatest challenge for you when using these devices and
how is it determined if it's properly placed?

Dr Bradley Knight: Well, one of the biggest challenges
honestly is not the procedure. It's identifying suitable candidates with people
that we think are good candidates who are going to benefit from it.
Unfortunately, as I mentioned, atrial fibrillation is increasing as patients
get older. We have a lot of patients who are in their 90s who don't tolerate
oral anticoagulation and would benefit from left atrial appendage closure. But
these patients also can be quite frail and have a lot of other comorbidities.
So, we're trying to identify patients who we think over the next few years will
benefit from a reduction in stroke.

From a technical standpoint, we have continued to do our
procedures under general anesthesia with transesophageal echo guidance. But we
now have a lot of experience with intracardiac echo guidance. So for those who
can't undergo TEE or general anesthesia, we can do these with ICE guidance
alone. We still, for most of our cases, use both TEE and ICE. And on top of
that, we have experience with the four-dimensional ICE, or realtime 3D ICE. We
place it in the left atrium at the time of the appendage closure procedure, and
it really gives us powerful anatomical guidance to place the device. This is an
anatomically driven procedure with imaging, both with TEE, with ICE and with
fluoroscopy. And we use all these imaging modalities to really optimize the
outcome.

The technical challenges are to find the right device for the
anatomy that the patient has. As we all know, the appendage is highly variable
in size and shape, and you can have some that kind of fold back on themselves
that we refer to as a chicken wing. Other shapes are more of just a straight
wind sock that you can place a plug device in more easily. So, every case is a
little bit different. The device that we have currently for the Watchman is the
Watchman FLX. It has significant advantages over the Watchman 2.5 device that was
available previously. We can now unsheath this into the shape of a ball and
then advance it and reposition it, recapture it. So, these technologies have
been under development for years, but even the last modification that was just
done a couple years ago has really greatly improved the safety and the success
rate of implanting a left atrial appendage closure device.

Melanie Cole, MS: Tell us, are you using this procedure
along with other adjuvant therapies or standalone? What's life like for the
patient after these procedures?

Dr Bradley Knight: Well, this is pretty much a
standalone procedure. There's some interest in doing this as a concomitant
procedure at the time of an AFib ablation. We've done that rarely. You know, it
adds complexity to an already complicated procedure if you did an ablation
procedure, catheter ablation for atrial fibrillation and then placed an
appendage closure. But it is tempting from the patient's standpoint, it's more
of one procedure. There's reimbursement challenges because that's not currently
an approach that's covered by most insurance companies. But from a patient
perspective, we have people stay overnight still after appendage closures. They
go home the next day. We usually recommend continuing oral anticoagulation for
45 days. Usually, this is with a NOAC and aspirin and, in 45 days, transition
them to aspirin and Plavix. That's how all the clinical trials really were
done. Actually, they were with Warfarin, but there's now approval and labeling
for dual anti-platelet therapy. And so, some patients who can't take NOACs will
go home on DAPT for six months. So, the challenge really right now, one of the
technical challenges is coming up with a safe anticoagulation or antiplatelet
regimen for the patients after the procedure.

Melanie Cole, MS: This is so interesting and what an
exciting time in your field. Dr. Knight, as we get ready to wrap up here, are
there any advancements on the horizon that are really exciting you in this
field? What do you see the future holding for stroke reduction in AFib
patients?

Dr Bradley Knight: While stroke reduction in AFib
patients is going to be a combination of medical therapy and device therapy,
there are actually some new oral anticoagulants, factor XI inhibitors, which
are showing promise in DVT prophylaxis in therapy. And so, I think there will
be some developments on the drug therapy arm. But from a device standpoint,
again, I've been involved in the appendage closure clinical trials for almost
20 years, and it's taken a long time to come up with new technologies. But
there are many new appendage closure devices under development that seem
promising. Even the currently available ones, the next iterations will be
improved.

As one example, one of the technical issues associated with the
current devices is device-related thrombi or DRT. There are some exciting
developments that were announced and published at the Harvard Annual Meeting
last month where the Watchman Device, the Watchman FLX device will be covered
with a fluoride-containing or fluoride fluorocarbon polymer overlying the face
of the device, which will lower the risk of device-related thrombi. So, it
would be great if we could actually implant these devices and really expose the
patients to very little anticoagulation afterwards and avoid any clots forming
on the devices themselves.

Melanie Cole, MS: Thank you so much, Dr. Knight, for
joining us and giving us such a comprehensive overview of those left atrial
appendage closure devices that you're using at Northwestern Medicine. And to
refer your patient or for more information, please visit our website at
breakthroughs for physicians.nm.org/cardiovascular to get connected with one of
our providers.

That concludes this episode of Better Edge, a Northwestern
Medicine Podcast for physicians. I'm Melanie Cole. Thanks so much for joining
us today.